# Determination of the motor patterning system for murine vocalizations with breathing

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $392,641

## Abstract

Our speech is composed of rhythmically timed elements, closely associated with syllables. This
feature is conserved across the animal kingdom, from fish to songbirds to monkeys, suggesting
that the tempo embedded within vocalizations is innately encoded. Indeed, others have
hypothesized that the rhythmicity of sound production is created by hardwired neural circuits in
the brainstem, but evidence to support this theory is lacking.
 Vocalizations are produced by the concerted activity of articulator (laryngeal and tongue)
and breathing muscles. Moreover, vocalizations must seamlessly integrate with or perhaps even
override the breathing rhythm. Given this, we hypothesized, as have others, that if a vocalization
motor patterning system existed, it would be anatomically and functionally connected to the neural
circuits for breathing in the brainstem. We also hypothesized that this same circuit would
intrinsically encode the rhythmicity of syllables within vocalizations. These two concepts - the
ability to autonomously pattern a rhythmic behavior - would define such a neural circuit as a
vocalization central pattern generator ‘CPG’, the first of its kind.
 To discovery this predicted vocalization CPG, we have studied the neural control of innate
murine neonatal cries, which are analogous to the cries of human infants. We found that murine
cries have a stereotyped syllabic structure and motor program. These two features of innate cries
suggest an underlying cry CPG. We have found a novel cluster of several dozen brainstem
neurons that are required to execute cries and premotor to multiple muscles used in vocalizations.
Here, we seek to characterize these neurons to determine if they are indeed a bonified
vocalization CPG. First, we will study if these neurons produce an autonomous oscillation as well
as the connectivity to correctly pattern the activity of muscles used in vocalizing. And then, we will
ectopically activate these neurons to find out if they are sufficient to elicit cries.
 The significance of this proposal is multifold. First-and-foremost, we will identify and
characterize a long-sought vocalization CPG. This forms a foundation to map the brain-wide
circuitry used in innate and learned vocalization. Second, we will determine how the vocalization
and breathing CPGs interact. An intriguing possibility is that our most vital neural circuit that
controls breathing might be overridden. In fact, even how distinct mammalian CPGs cooperate to
produce complex behaviors remains poorly understood. And ultimately, this work will enable
dissection of the mechanisms of speech pathologies in autism spectrum disorders as well as
apraxia, dysarthria, or stutter.

## Key facts

- **NIH application ID:** 10422658
- **Project number:** 1R01NS126400-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Kevin Yackle
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $392,641
- **Award type:** 1
- **Project period:** 2022-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10422658

## Citation

> US National Institutes of Health, RePORTER application 10422658, Determination of the motor patterning system for murine vocalizations with breathing (1R01NS126400-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10422658. Licensed CC0.

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